Cancer Immunotherapy and Uveitis: Balancing Anti-Tumor Immunity and Ocular Autoimmunity.

Immune checkpoint inhibitors and targeted therapies are two classes of pharmacologic therapies used to treat metastatic malignancy by amplifying the immune system activity against cancerous cells. However, these drugs can consequently cause immune-related adverse events (irAEs). Albeit rare, cases of ocular IRAEs occurring among patients taking these drugs have been documented in literature, including a spectrum of uveitis findings. The classes of immune checkpoint inhibitors explored here include anti-CTLA4 (ipilimumab), anti-PD-1 (pembrolizumab, nivolumab) and anti-PDL-1 (atezolizumab, avelumab, durvalumab). Targeted therapies include the MEK inhibitors (trametinib) and BRAF enzyme inhibitors (dabrafenib, vemurafenib), both of which are involved in the MAPK/ERK signaling pathway responsible for cell proliferation. Reported cases of ocular irAEs caused by these drugs include anterior uveitis, posterior uveitis, panuveitis, and Vogt-Koyanagi-Harada (VKH)-like syndrome. Treatment can be determined on a case-by-case basis and depending on the severity of the irAE, may include temporary cessation of the offending drug, local corticosteroids, or systemic corticosteroids. Although the mechanism by which these ocular toxicities occur is not clearly elucidated, it is hypothesized that they are secondary to increased activity of auto-reactive T-cells. Further investigation into mechanisms underlying these inflammatory findings are relevant for cancer targeting, as well as insights into ocular autoimmune diseases.